PROJECT SUMMARY/ABSTRACT Sensorineural hearing loss (SNHL) can occur as a result of dysfunction of outer hair cells, inner hair cells, auditory-nerve fibers or synapses. However, standard clinical techniques are limited in their ability to differentiate these dysfunctions because they focus on threshold elevation and thus provide insufficient information about suprathreshold auditory dysfunction, which has greater ecological validity than threshold elevation. SNHL that does not elevate thresholds, and therefore would be missed by standard clinical techniques, is sometimes referred to as ?hidden hearing loss? (HHL). Recent animal studies suggest that noise-induced synaptopathy may underlie HHL and may be the cause of suprathreshold hearing deficits, such as difficulty understanding speech in noise. However, there is limited research to support the diagnosis of HHL in humans beyond reports that some individuals have suprathreshold hearing deficits that cannot be predicted from their audiograms. Understanding HHL in humans will require the use of measurements of auditory function that are specific to the location of the dysfunction in the auditory pathway, including the specific group of auditory-nerve fibers (low vs. high spontaneous-rate fibers) underlying the dysfunction. The long-term goals of this research program are to improve our understanding of suprathreshold hearing deficits and to develop intervention strategies that ameliorate these deficits. The immediate goal of this proposal is to establish a theoretical framework for the development of diagnostic methods for HHL in humans. Unfortunately, a ?gold standard? does not exist because synaptopathy cannot be directly observed in humans. Consequently, our approach is to develop a statistical model of HHL that describes the relationship and interdependence between specific behavioral and physiological measures of auditory function that are thought to be indicative of HHL and measures that reflect the functional integrity of sites along the auditory pathway. The goal will be achieved by pursuing three aims: (1) Develop a statistical model of HHL for individuals with normal hearing, (2) Develop a statistical model of HHL for individuals with clinical hearing loss caused by noise exposure, and (3) Validate a predictive model of HHL and demonstrate its relation to speech understanding in noise. We will establish a functional definition of HHL as a component of the variability in measures impacted by HHL that is not due to audiometric threshold. We will then create a statistical model that relates this estimate of HHL to measures that reflect sites of dysfunction along the auditory pathway. Through the aims, we will test the hypothesis that HHL accounts for some of the variability in suprathreshold measures of auditory function. The proposed research will lead to evidence-based models of suprathreshold auditory dysfunction that are capable of predicting hearing deficits, provide further insights into suprathreshold auditory deficits and improve our understanding of potential mechanisms underlying hearing and listening difficulties. The ability to diagnose HHL in the clinic will usher in new methods for clinical evaluation and may lead to better remediation techniques of hearing loss.